Study On Budesonide Thermosensitive Gel Enema

Object:For the defects of enema administration preparation,our group used temperature-sensitive gel enema as the carrier of budesonide rectal preparation to have broad-spectrum antibacterial [1,2],help wound healing [3,4],and facilitate hemostasis [5,6].Chitosan and ?-glycerophosphate as a thermosensitive gel material,konjac as a bioadhesive,Tween-80 as a budesonide cosolvent,developed a suitable enema for administration and far The budesonide thermosensitive gel enema solution can be used for a long-lasting effect.This paper mainly reports the formulation screening and optimization of budesonide thermosensitive gel enema,rheological characterization,in vitro release characteristics,stability,and retention in vivo.Method:The budesonide thermosensitive gel enema solution was prepared.Based on the single factor investigation,the drug release rate was used as the evaluation index of Tween-80 dosage screening.The pre-gelation viscosity,gelation temperature and p H were used as the evaluation indexes for the formulation optimization.The star-point design-effect surface method was used to screen the dosage of chitosan,?-glycerophosphate and konjac in the prescription.The in vitro release of budesonide thermosensitive gel enema was investigated by dynamic dialysis.The budesonide content in the release medium was determined by high performance liquid chromatography.The release mechanism was explored by simulation fitting.Investigate the appearance of the dexamethasone gel-sensitive enema solution at different temperatures(4?,25?,60?),strong light conditions,viscosity before gelation,p H,gelation temperature,stability of drug content,investigate The budesonide thermosensitive gel enema solution simulates the appearance and shape under the commercial packaging and storage conditions,the viscosity before gelation,the p H,the gelation temperature,the stability of the drug content,and the influencing factors.Kunming mice were randomly divided into the temperature-sensitive gel enema group and the common enema group.They were fasted for 24 hours,and could not be forbidden.The animals were given enema with temperature-sensitive gel enema and fluorescent enema with fluorescent markers.At the 0,1st,2nd,4th,6th,8th,10 th,and 12 th hour of administration,the retention of the drug in the body was observed by a small animal imager system.Results:The optimal ratio of the prescription matrix was chitosan:?-glycerophosphate: konjac: Tween-80=1.4:23.78:0:0.025.The budesonide thermosensitive gel enema solution was prepared according to the preferred formulation,and the gelation temperature was about 35.2?,the viscosity before gelation was about 493.66 m Pa·s,and the p H was 7.4.The rheological parameters of the optimized formulation under different conditions were determined by dynamic rheological experiment.The results showed that the gel has good temperature response sensitivity,low viscosity at room temperature,good fluidity,easy to be administered,and can be completed in the colon environment.The viscosity is increased to form a gel with stable pseudoplastic fluid properties.The results of in vitro release showed that budesonide released 81.2% at12 h and 70.7% at 8h in the temperature-sensitive gel,which was more release than normal budesonide enema.The release curve of the temperature sensitive gel within 12 h has the best fit with the Higuchi simulation equation: Q=22.976t^(1/2)+ 4.5468,R2 = 0.99,budesonide thermosensitive gel enema mainly releases by diffusion mechanism.The test results of influence factor test show that the properties,p H value and glue of the preparation Condensation temperature,content stability,high temperature(60?)temperature sensitive gel enema gel,placed at room temperature(25?)irreversible,light(4500Lx ± 500Lx),high temperature(60?)affect the pre-gelation viscosity of the preparation,The drug content indicates that the preparation should be stored in a cool place.The long-term stability test results have shown that the preparation is kept at room temperature for 3 months under the light,and the stability is good.All the indexes are within the reference range,which provides a basis for preparation preparation and storage conditions,and is also a follow-up accelerated experiment.And provide conditions for long-term experimental conditions to provide a basis for the development of the drug's effective period.The results of In vivo retention test showed that the temperature-sensitive gel enema solution can stay in the body for at least 12 hours,and at the same time Fluorescence signal was observed at the administration site.After 1 hour of administration,the fluorescent signal was observed in the abdominal fluid of the mouse.At the 4th hour,almost no fluorescence signal was observed,and only the fluorescent signal was observed at the administration site.The temperature sensitive gel enema has good ductility and retention.Conclusion:In summary,the formulation and preparation process of budesonide thermosensitive gel enema solution developed by the subject is suitable,the temperature sensitivity is good,and it has a certain sustained release effect,which can effectively reduce drug leakage and improve the residence time of the drug in the lesion.Therefore,this study provides a scientific basis for the development of budesonide for rectal topical preparations,and is expected to improve the efficacy of budesonide common enema for distal colitis and provide a more therapeutic option for patients with ulcerative colitis.